Regeneron Pharmaceuticals has announced positive topline results from a placebo-controlled phase 2/3 study evaluating fasinumab in patients with moderate-to-severe osteoarthritis pain of the hip or knee who have a history of inadequate pain relief or intolerance to current analgesic therapies.
At 16 weeks, patients treated with all four doses of fasinumab, an investigational nerve growth factor (NGF) antibody, demonstrated a statistically significant improvement in pain relief, the primary endpoint of the study, as well as improvements in the secondary measure evaluating physical function.
The U.S. study enrolled 421 adult patients with moderate-to-severe osteoarthritis of the hip or knee who had a history of inadequate pain relief or intolerance to acetaminophen and at least one oral nonsteroidal anti-inflammatory drug and an opioid. Patients in the study were experiencing significant pain at baseline with an average pain score of 6.3 on a 10-point scale. Patients were evaluated for pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in addition to other measures. Patients were randomized to one of five treatment groups in a 1:1:1:1:1 fashion: fasinumab 1 mg, 3 mg, 6 mg, 9 mg, or placebo, all delivered subcutaneously every four weeks through week 12, with the primary efficacy measured at week 16. Following week 16, patients are being studied for an additional 20 weeks off treatment.
On the primary endpoint, fasinumab-treated patients reported less pain at 16 weeks when compared to placebo on the 10-point WOMAC subscale for pain.
The safety analysis includes all results at the time of the primary efficacy analysis; complete data will be reported when all patients complete the full 36 weeks. Overall incidence of adverse events, including serious and severe events, was similar across the fasinumab groups and placebo. As expected with antibodies to NGF, there was an increase in certain neuromusculoskeletal adverse events in the fasinumab treatment groups (17% combined fasinumab; 6% placebo), including arthralgia, paresthesia, hypoesthesia, and peripheral edema.
Because of prior concerns with other anti-NGF therapies regarding the possible risk of joint damage, the study incorporated extensive imaging and analyses, at baseline and during the study, of index and nonindex joints, with particular focus on subchondral insufficiency fractures (SIF), osteonecrosis (ON), and rapidly progressive osteoarthritis (RPOA). Approximately 2% of screened subjects were excluded from participation based on findings of SIF or ON on baseline imaging exams.
During the study period, there were no cases of ON. There was one case of SIF in placebo and zero, two, zero, and four cases of SIF in the 1-mg, 3-mg, 6-mg, and 9-mg fasinumab dose groups, respectively. There was one case of RPOA in each of the 3-mg, 6-mg, and 9-mg fasinumab dose groups. A modest increase in the lab value for bone-specific alkaline phosphatase, a marker of osteoblast activity, was noted in fasinumab-treated patients; there was no increase in liver alanine transaminase and aspartate transaminase enzymes.
Source: Regeneron Pharmaceuticals; May 2, 2016.